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University of Toronto St. George
Yue Li

14 THE CARDIOVASCULAR SYSTEM: BLOOD VESSELS, BLOOD FLOW, AND BLOOD PRESSURE Physical Laws Governing Blood Flow and Blood Pressure  The flow rate of a liquid (the volume flowing per unit or time) through a pipe is directly proportional to the difference between the pressures at the two ends of the pipe (the pressure gradient) and inversely proportional to the resistance of the pipe.  FLOW = pressure gradient / resistance = P/R  The quantity P, the size of the pressure gradient, represents the driving force that pushes the flow of liquid through a pipe; the quantity R, the resistance, is a measure of the various factors that hinder the flow of liquid through a pipe. PRESSURE GRADIENTS IN THE CARDIOVASCULAR SYSTEM  Whenever there is a difference in pressure between two locations, the pressure gradient drives the flow from a region of higher pressure to one of lower pressure, or down the pressure gradient.  The driving force for bulk flow is always a pressure gradient, and the direction of flow is always down the gradient from a region of greater pressure to a region of lower pressure.  THE ROLE OF RPESSURE GRADIENTS IN DRIVING BLOOD FLOW o The primary function of the heart is to generate the pressure that drives the flow of blood through the vasculature. o By pumping blood into the arteries, the heart raises, mean arterial pressure, which creates a difference in pressure between the arteries and veins that drives the flow of blood. o The vertical distance from the vessel to the surface of the liquid, the so-called hydrostatic column, determines the pressure at either end of the vessel. Pressure also depends on density. o A higher hydrostatic column corresponds to a greater pressure. o If the difference between the levels remains constant, the flow does not change.  PRESSURE GRADIENTS ACROSS THE SYSTEMIC AND PULMONARY CIRCUITS o Mean arterial pressure (MAP, the average pressure in the aorta throughout the cardiac cycle) is about 85mm Hg. o Central venous pressure (CVP) is approximately 2-8 mm Hg, and the pressure in the vena cava just outside the right atrium is approximately 0 mm Hg. o The difference between the MAP and CVP is the pressure gradient that drives blood flow through the systemic circuit. o Because central venous pressure is so small, we ignore. o The pressure gradient P driving blood flow through the systemic circuit is equated to the mean arterial pressure. o Blood flow through the pulmonary circuit is also driven by a pressure gradient – the difference between the pressure in the pulmonary arteries and the pressure in the pulmonary veins. o Pressure gradient is smaller than the one that goes through the systemic circuit because pulmonary arterial pressure is lower than aortic pressure. o Pulmonary arterial pressure = 15mm Hg. Aorta = 85mm Hg. Pulmonary venous pressure = 0mm Hg. o If the pressure gradient to drive blood flow through the pulmonary circuit is relatively low, then the resistance must also be low. RESISTANCE IN CARDIOVASCULAR SYSTEM  If the pressure gradient in the pulmonary circuit is lower than that in the systemic circuit, to have the same blood flow, the pulmonary circuit offers less resistance, so a smaller pressure gradient can achieve the same flow.  RESISTANCE OF INDIVIDUAL BLOOD VESSELS o A vessel with higher resistance yields a lower flow. Blood flow is greater when resistance is lower because it is easier for blood to flow. o Resistance depends on the physical dimensions of the tube and the properties of the fluid flowing through it – the tube’s radius and length, and the fluid’s viscosity. 1. Vessel radius: as radius decreases, resistance increases. Vasoconstriction: decrease in blood vessel radius. Vasodilation: increase in vessel radius. 2. Vessel length: longer vessels have greater resistance, but resistance is rarely due to changes in vessel length. 14 THE CARDIOVASCULAR SYSTEM: BLOOD VESSELS, BLOOD FLOW, AND BLOOD PRESSURE 3. Blood viscosity: vascular resistance increases as viscosity increases. Determined by the concentration of cells and proteins in the blood. Overview of the Vasculature  Arteries and smaller arterioles carry blood from the heart and to capillaries, which are drained by venules, and then larger veins, which return the blood to the heart.  The arterioles, capillaries, and venues can be seen only with the aid of a microscope and, therefore, are called microcirculation.  Lumen: blood vessels’ hollow interior; it is lined by a layer of epithelium called endothelium.  Capillaries, consists of a layer of endothelial cells and a basement membrane.  The walls of all other blood vessels contain various amounts of smooth muscle and fibrous and/or elastic connective tissue. Within the fibrous connective tissue are extracellular fibers made of a protein called collagen, which lends tensile strength to vessel walls.  Elastic connective tissue contains fibers of a highly stretchable extracellular protein called elastin, which enables blood vessels to expand or contract as the pressure of blood within them changes. Arteries  Arteries conduct blood away from the heart and toward the body’s tissue.  Aorta (largest artery) has an internal diameter of 12.5mm and a wall that is 2mm thick.  The smaller arteries that branch off the aorta have internal diameters ranging from 2mm to 6mm and a wall thickness of about 1mm, and this branch into yet smaller-diameter arteries.  The walls of large arteries contain large amounts of elastic and fibrous tissue, enabling arteries to withstand relatively high blood pressures, which are higher in these vessels than anywhere else in the vasculature.  As the arteries branch into smaller arteries, the amount of elastic tissue in the walls decreases while the amount of smooth muscle increases.  Arteries less than 0.1mm are called muscular arteries (lose most of their elastic properties). ARTERIES: A PRESSURE RESERVOIR  The thickness of arterial walls, coupled with the relative abundance of elastic tissue, gives arteries both stiffness and the ability to expand and contract as the blood pressure rises and falls with each heartbeat.  As pressure reservoirs, it ensures a continual, smooth flow of blood through the vasculature even when the heart is not pumping blood (diastole).  This elastic force is stored such that during diastole, when no more blood is entering the arteries, the walls passively recoil inward, propelling blood forward.  The pulse is caused by a pressure wave that travels along the arteries in response to blood being pushed into the arteries during systole, causing the arterial wall to expand.  Compliance: a measure of the relationship between the pressure and volume changes.  In vessels with low compliance, such as arteries, a small increase in blood volume causes a large increase in blood pressure (or a large increase in pressure causes only a small degree of expansion of the blood vessel walls).  When the heart ejects blood into the arteries during systole, and causes them to expand, the resulting rise in pressure is greater than it would be it arteries’ compliances were higher.  The low compliance of arteries is a function of elasticity of the vessel walls. ARTERIAL BLOOD PRESSURE  Arterial blood pressure: pressure in the aorta; pressure in the aorta doesn’t stay elevated because during diastole, blood quits flowing into the aorta yet continues to flow out, which causes a slow decline in arterial blood pressure to a minimum just prior to the next systole.  The maximum pressure that occurs during systole is called the systolic pressure, and the minimum pressure that occurs during diastole is called the diastolic pressure.  The average arterial pressure during the cardiac cycle is the mean arterial pressure (MAP).  MEASURING ARTERIAL BLOOD PRESSURE 14 THE CARDIOVASCULAR SYSTEM: BLOOD VESSELS, BLOOD FLOW, AND BLOOD PRESSURE o Pressure is usually measured in the brachial artery, which runs through the upper arm. o Pressure measured in this manner is close to the aortic pressure because the brachial artery is not far from the heart, and is also at about the same height as the aorta. o Use a sphygmomanometer, which consists of an inflatable cuff and a pressure-measuring device that displays air pressure inside the cuff, and they use a stethoscope placed over that brachial artery to listen for sounds produced by turbulent blood flow. o To measure blood pressure, the technician places the cuff around the upper arm and inflates it to increase the cuff pressure. o This pressure is transmitted through the tissue of the arm to the brachial artery, which runs to the lower arm. . o The technician increases cuff pressure until it is above systolic arterial pressure, which causes the artery to collapse, stopping blood flow. Then allow the cuff pressure to fall slowly. o When cuff pressure drops to where it is just slightly below systolic arterial pressure, the artery opens briefly with each heartbeat when the pressure inside the artery is higher than that outside it, which forces the vessel open. o Turbulence creates sounds, called Korotkoff sounds, which can be heard through the stethoscope. When the Korotkoff sounds first appear, the technician notes the cuff pressure and records it as systolic arterial pressure. o Eventually, cuff pressure falls just below diastolic arterial pressure, from which point the artery stays open throughout the entire cardiac cycle because pressure inside the artery is always higher than that outside it. o The technician notes the cuff pressure where sounds first disappear and records it as the diastolic arterial pressure. o Healthy individual is 110/70 (SP/SP) Arterioles  The smallest arteries branch into even smaller arterioles, which lead either into a capillary bed or into metarterioles, which then lead into capillary beds.  The walls of arterioles contain little elastic material but have an abundance of circular smooth muscle that forms rings around the arterioles. ARTERIOLES AND RESISTANCE TO BLOOD FLOW  The arterioles are the blood vessels that provide the greatest resistance to blood flow.  As blood flows from arteries to veins, pressure decreases, gradually.  A difference in pressure across any portion of the vasculature is called the pressure drop across that part.  The largest pressure drop occurs along the arterioles: 75-80 mmHg to 35-40 mmHg. It is related to high resistance of arterioles.  The pressure becomes less pulsatile as it moves through the vasculature.  The major function of arterioles is to serve as points of control for regulating resistance to blood flow, which serves 2 functions: 1) controlling blood flow to individual capillary beds, 2) regulating mean arterial pressure. INTRINSIC CONTROL OF BLOOD FLOW DISTRIBUTION TO ORGANS  REGULATION IN RESPONSE TO CHANGES IN METABOLIC ACTIVITY: ACTIV HYPEREMIA o Vascular smooth muscle cells in arterioles are sensitive to conditions in extracellular fluid and respond to changes in the concentrations of a wide variety of chemical substances. o Arteriolar smooth muscle either contracts or relaxes depending on whether concentrations of particular substances rise or fall. o Changes associated with increased metabolic activity generally cause vasodilation, whereas changes associated with decreased metabolic activity induce vasoconstriction. o When blood flow is matched to the tissue’s metabolic needs, the concentrations of oxygen and carbon dioxide in the tissue are in a steady state: the rate at which oxygen enters the tissue from the blood equals the rate at which it is consumed by the cells, and the rate of carbon dioxide entering the blood equals the rate at which it is produced by the cells. 14 THE CARDIOVASCULAR SYSTEM: BLOOD VESSELS, BLOOD FLOW, AND BLOOD PRESSURE o Metabolic rate increases, it causes a decrease in tissue oxygen (hypoxia) and an increase in tissue carbon dioxide. o Initially blood blow is insufficient to keep up with metabolic demand, a condition called ischemia. The decrease in oxygen and the increase in carbon dioxide both act on arteriolar smooth muscle, causing it to relax. o Increase in blood flow following an increase in metabolic activity is termed active hyperemia (intrinsic control). As a result of this increase in blood flow, the oxygen delivery to the tissue and carbon dioxide removal from the tissue increase, and eventually a new steady state is achieved.  REGULATION IN RESPONSE TO CHANGES IN BLOOD FLOW: REACTIVE HYPEREMIA o Tissue oxygen and metabolite concentrations can also change as a result of changes in blood flow. o If blood flow is blocked or reduced below adequate levels for any reason, the oxygen concentration falls and the carbon dioxide level rises because rates of oxygen consumption and carbon dioxide production exceed rates of delivery and removal, respectively. o Both induce vasodilation and a reduction in vascular resistance, which tend to increase blood flow. o Once blockage is removed, the rate of flow will be higher than normal and will remain elevated until excess metabolites are removed and tissue oxygen concentration is restored to normal (reactive hyperemia). o If blood flow rises above what is required for metabolic needs, intrinsic control mechanisms will induce vasoconstriction and a reduction in blood flow.  REGULATION IN RESPONSE TO STRETCH OF ARTERIOLAR SMOOTH MUSCLE: MYOGENIC RESPONSE o Certain tissues contain arteriolar smooth muscle called stretchsensitive fibers (responsive to stretch, when pressure of blood within the arterioles increases) o A change in vascular resistance that occurs in response to stretch of blood vessels, and that does not require the action of sympathetic nerves, bloodborne hormones, or other chemical agents, is a myogenic response. o Perfusion pressure: the pressure gradient that drives blood flow through a given organ or tissue. It is increases in an organ or tissue, blood flow increases and arteriolar pressure rises, which stretches the arteriolar walls. o In arterioles containing stretchsensitive smooth muscle, the muscle fibers then contract, which increases the arteriole’s resistance and decreases the flow of blood through it. o A decrease in perfusion pressure brings about the opposite response – vasodilation and an increase in blood flow. o The variable that remains constant in myogenic control is blood flow. Local regulation that tends to keep blood flow constant is called flow autoregulation. o These changes in concentration cause vasoconstriction, which reduces blood flow. But the increase in perfusion pressure also increases stretch of arteriolar walls, which in turn induces vasoconstriction and a reduction in blood flow.  REGULATION BY LOCALLY SECRETED CHEMICAL MESSENGERS o Blood vessel endothelial cells or cells in surrounding tissue secrete chemicals that effect contractile activity of vascular smooth muscle. o Nitric oxide, which is released on a continual basis by endothelial cells in arterioles and acts on smooth muscle to promote vasodilation. o Substances produced by inflamed tissues, such as bradykinin and histamine stimulate nitric oxide synthesis. o Prostacyclin, an eicosanoid that functions in preventing blood clots. Independent Regulation of Blood Flow  Blood flow to organs is independently regulated by comparing the proportions of total blood flow each organ receives at rest and during exercise.  If blood flow to organs were not regulated independently, the proportion of CO each organ receives would remain constant, and blood flow to every organ would rise as cardiac output rises during exercise.  When the body makes a transition from rest to exercise, intrinsic controls divert blood away from the liver and gastrointestinal tract and toward the muscles, which have high metabolic demands during exercise.  The increased blood supply to muscles provides the oxygen and nutrients needed to generate contractile force. 14 THE CARDIOVASCULAR SYSTEM: BLOOD VESSELS, BLOOD FLOW, AND BLOOD PRESSURE Capillaries and Venules CAPILLARY ANATOMY  Capillaries are the smallest blood vessels, measuring only 1mm long and 5-10 m, consisting of a single layer of endothelial cells surrounded by a basement membrane.  The small diameter and thin wall provide a small diffusion distance between blood and the surrounding interstitial fluid.  Extensive branching results in 10-40 billion capillaries. A surface area of 600 sq. meters. Almost all cells of the body are within 1mm of a capillary.  As blood enters capillary beds, the velocity of blood flow decreases.  Velocity of blood flow through the capillaries is about 0.1 mm/sec, allowing approximately 1 sec for exchange between blood and tissue to take place.  Leakiness of the capillary wall enhances exchange between blood and tissue. Most capillaries, however, are considerably “leaky” and are classified as either continuous or fenestrated, based on their degree of “leakiness”.  CONTINUOUS CAPILLARIES o Continuous capillaries have endothelial cells joined together such that the spaces between them are relatively narrow. They are highly permeable to substances having small molecular sizes and/or high lipid solubility and are somewhat less permeable to small water-soluble substances. o The permeability of continuous capillaries to proteins and other macromolecules I very low because these substances can neither readily cross membranes of endothelial cells, nor easily penetrate the gaps between cells.  FENESTRATE
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